Treatment of pituitary-dependent Cushing's disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial.
BACKGROUND
There is currently no medical therapy for Cushing's disease that targets the pituitary adenoma. Availability of such a medical therapy would be a valuable therapeutic option for the management of this disorder.


OBJECTIVE
Our objective was to evaluate the short-term efficacy of the novel multireceptor ligand somatostatin analog pasireotide in patients with de novo, persistent, or recurrent Cushing's disease.


METHODS
We conducted a phase II, proof-of-concept, open-label, single-arm, 15-d multicenter study.


METHODS
Thirty-nine patients with either de novo Cushing's disease who were candidates for pituitary surgery or with persistent or recurrent Cushing's disease after surgery without having received prior pituitary irradiation.


METHODS
Patients self-administered sc pasireotide 600 microg twice daily for 15 d.


METHODS
Normalization of urinary free cortisol (UFC) levels after 15 d treatment was the main outcome measure.


RESULTS
Of the 29 patients in the primary efficacy analysis, 22 (76%) showed a reduction in UFC levels, of whom five (17%) had normal UFC levels (responders), after 15 d of treatment with pasireotide. Serum cortisol levels and plasma ACTH levels were also reduced. Steady-state plasma concentrations of pasireotide were achieved within 5 d of treatment. Responders appeared to have higher pasireotide exposure than nonresponders.


CONCLUSIONS
Pasireotide produced a decrease in UFC levels in 76% of patients with Cushing's disease during the treatment period of 15 d, with direct effects on ACTH release. These results suggest that pasireotide holds promise as an effective medical treatment for this disorder.
Boscaro
M
M
Division of Endocrinology, Polytechnic University of Marche, 60126 Ancona, Italy.
Ludlam
W H
WH
Atkinson
B
B
Glusman
J E
JE
Petersenn
S
S
Reincke
M
M
Snyder
P
P
Tabarin
A
A
Biller
B M K
BM
Findling
J
J
Melmed
S
S
Darby
C H
CH
Hu
K
K
Wang
Y
Y
Freda
P U
PU
Grossman
A B
AB
Frohman
L A
LA
Bertherat
J
J
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy* / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives
D001786:Blood Glucose; D007328:Insulin; D009842:Oligopeptides; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; C517782:pasireotide; D006854:Hydrocortisone